Altered action of glucagon on human liver in type 2 (non-insulin-dependent) diabetes mellitus.

Altered action of glucagon on human liver in type 2 (non-insulin-dependent) diabetes mellitus.
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胰高血糖素对 2 型(非胰岛素依赖型)糖尿病患者肝脏的作用发生改变。

DOI:
10.1007/bf00299025
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发表时间:
1987
期刊:
影响因子:
8.2
通讯作者:
Livingston,JN
Livingston,JN
中科院分区:
医学1区
文献类型:
--
作者:
Arner,P;Einarsson,K;Ewerth,S;Livingston,JN

文献摘要

相似文献

胰高血糖素可能在显性2型(非胰岛素依赖型)糖尿病的代谢紊乱中发挥作用。因此,我们通过研究7例空腹高血糖和血浆胰高血糖素升高2倍的2型糖尿病患者肝膜中对腺苷酸敏感的腺苷酸环化酶系统,评估了胰高血糖素作用的早期步骤。与年龄、性别和体重相匹配的7名对照受试者进行了比较。两组中胰高血糖素受体结合几乎相同。然而,糖尿病患者的膜中腺苷酸环化酶活性有明显的改变。与对照活性相比,该活性降低了35-50%。基础环化酶活性,以及用胰高血糖素或试剂(i.例如,氟化钠和毛喉素),作用于胰高血糖素受体以外,显著降低(P<0.05,P <0.001)。总之,不受控制的2型糖尿病与人肝脏中对腺苷酸敏感的腺苷酸环化酶的反应性的全面丧失有关,这显然是由受体后改变引起的。这种变化可能提供了一种降低2型糖尿病高血糖症影响的机制。
Glucagon may play a role in the metabolic derangements of overt Type 2 (non-insulin-dependent) diabetes mellitus. We therefore have evaluated the early steps in glucagon action by investigating the hormone-sensitive adenylyl cyclase system in liver membranes from seven Type 2 diabetic patients with fasting hyperglycaemia and two-fold elevations in plasma glucagon. The comparison was made with seven control subjects matched for age, sex and body weight. Glucagon receptor binding was almost identical in the two groups. There were, however, marked alterations in the adenylyl cyclase activity in membranes from the diabetic patients. This activity was reduced by 35–50% when compared to control activity. Basal cyclase activity, as well as the activity after stimulation with glucagon or with agents (i. e., sodium fluoride and forskolin) that act beyond the glucagon receptor, was significantly decreased (p<0.05,p<0.001 respectively). In conclusion, uncontrolled Type 2 diabetes in associated with an over-all loss of responsiveness of the hormone-sensitive adenylyl cyclase in human liver, which apparently results from post-receptor alterations. This change may provide a mechanism for reducing the effect of hyperglycagonaemia in Type 2 diabetes mellitus.